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This study aims to explore the relationship between radiological imaging and genomic characteristics in clear cell renal cell carcinoma (ccRCC), focusing on the expression of adipose differentiation-related protein (ADFP) detected through computed tomography (CT). The goal is to establish a radiogenomic lipid profile and understand its association with tumor characteristics. Data from The Cancer Genome Atlas (TCGA) and the Cancer Imaging Archive (TCIA) were utilized to correlate imaging features with adipose differentiation-related protein (ADFP) expression in ccRCC. CT scans assessed various tumor features, including size, composition, margin, necrosis, and growth pattern, alongside measurements of tumoral Hounsfield units (HU) and abdominal adipose tissue compartments. Statistical analyses compared demographics, clinical–pathological features, adipose tissue quantification, and tumoral HU between groups. Among 197 patients, 22.8% exhibited ADFP expression significantly associated with hydronephrosis. Low-grade ccRCC patients expressing ADFP had higher quantities of visceral and subcutaneous adipose tissue and lower tumoral HU values compared to their high-grade counterparts. Similar trends were observed in low-grade ccRCC patients without ADFP expression. ADFP expression in ccRCC correlates with specific imaging features such as hydronephrosis and altered adipose tissue distribution. Low-grade ccRCC patients with ADFP expression display a distinct lipid metabolic profile, emphasizing the relationship between radiological features, genomic expression, and tumor metabolism. These findings suggest potential for personalized diagnostic and therapeutic strategies targeting tumor lipid metabolism. [ABSTRACT FROM AUTHOR]

This study aims to explore the relationship between radiological imaging and genomic characteristics in clear cell renal cell carcinoma (ccRCC), focusing on the expression of adipose differentiation-related protein (ADFP) detected through computed tomography (CT). The goal is to establish a radiogenomic lipid profile and understand its association with tumor characteristics. Data from The Cancer Genome Atlas (TCGA) and the Cancer Imaging Archive (TCIA) were utilized to correlate imaging features with adipose differentiation-related protein (ADFP) expression in ccRCC. CT scans assessed various tumor features, including size, composition, margin, necrosis, and growth pattern, alongside measurements of tumoral Hounsfield units (HU) and abdominal adipose tissue compartments. Statistical analyses compared demographics, clinical–pathological features, adipose tissue quantification, and tumoral HU between groups. Among 197 patients, 22.8% exhibited ADFP expression significantly associated with hydronephrosis. Low-grade ccRCC patients expressing ADFP had higher quantities of visceral and subcutaneous adipose tissue and lower tumoral HU values compared to their high-grade counterparts. Similar trends were observed in low-grade ccRCC patients without ADFP expression. ADFP expression in ccRCC correlates with specific imaging features such as hydronephrosis and altered adipose tissue distribution. Low-grade ccRCC patients with ADFP expression display a distinct lipid metabolic profile, emphasizing the relationship between radiological features, genomic expression, and tumor metabolism. These findings suggest potential for personalized diagnostic and therapeutic strategies targeting tumor lipid metabolism.

Previously, we identified differentially expressed proteins, including ADFP, between lung adenocarcinoma (LAC) tissue and paired normal bronchioloalveolar epithelium. In this study, we investigated the role of ADFP in LAC. ADFP levels in the serum of patients with lung cancer and benign diseases were measured by enzyme‐linked immunosorbent assays (ELISA). shRNA was used to knock‐down or overexpress ADFP in A549 and NCI‐H1299 cells. The biological function of ADFP and its underlying mechanisms was evaluated in vivo and in vitro. ADFP was highly expressed in the serum of lung cancer patients, especially those with LAC. ADFP promoted cell proliferation and up‐regulated the p‐Akt/Akt ratio in A549 and NCI‐H1299 cells in vitro. Furthermore, in nude mice, ADFP promoted tumour formation with high levels of p‐Akt/Akt, Ki67 and proliferating cell nuclear antigen (PCNA). Similar to the effect of ADFP knock‐down, MK‐2206 (a phosphorylation inhibitor of Akt) reduced A549 and NCI‐H1299 cell proliferation. In ADFP‐overexpressing A549 and NCI‐H1299 cells, proliferation was suppressed by MK‐2206 and returned to the control level. ADFP did not regulate invasion, migration or adhesion in LAC cells. Together, these results suggest that ADFP promotes LAC cell proliferation in vitro and in vivo by increasing Akt phosphorylation level. [ABSTRACT FROM AUTHOR]

ABSTRACT Adipose differentiation-related protein (ADFP) is a fatty acid-binding protein that can promote the absorption of long-chain fatty acids. However, few results have been published regarding its role in Yunnan Native chicken breeds. The aim of this study was to determine ADFP gene tissue-specific expression in Piao chickens (PC) and Wuliangshan black-bone chickens (WBC) by RT-qPCR. The ontogenetic expression levels of the ADFP gene were significantly different during growth and development phases in the subcutaneous fat, liver, and pectoralis muscle of PC, and in the subcutaneous fat, liver, and pectoralis muscle of WBC (p0.05). The results suggest ADFPdifferential expression in the liver and pectoral muscles of PC and WBC during the growth and development phases (p

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Although neutral lipid storage droplets are ubiquitous in eukaryotic cells, very little is known about how their synthesis and turnover are controlled. Adipocyte differentiation-related protein (ADRP; also known as adipophilin) is found on the surface of lipid droplets in most mammalian cell types. To learn how ADRP affects lipid storage, we stably expressed the protein in human embryonic kidney 293 (HEK 293) cells, which express little endogenous ADRP. As expected, ADRP was targeted to the surface of lipid droplets and caused an increase in triacylglycerol (TAG) mass under both basal and oleate-supplemented conditions. At least part of the increased mass resulted from a 50% decrease in the rate of TAG hydrolysis in ADRP-expressing cells. Furthermore, ADRP expression increased the fraction of total cellular TAG that was stored in lipid droplets. ADRP expression induced a striking decrease in the association of adipose triglyceride lipase (ATGL) and mannose-6-phosphate receptor tail-interacting protein of 47 kDa with lipid droplets and also decreased the lipid droplet association of several other unknown proteins. Transient expression of ADRP in two other cell lines also reduced the lipid droplet association of catalytically inactive ATGL. We conclude that the reduced lipid droplet association of ATGL and/or other lipases may explain the decrease in TAG turnover observed in ADRP-expressing HEK 293 cells.

Hereditary sensory neuropathy type 1 (HSN-1) is an autosomal dominant neurodegenerative disease caused by missense mutations in the SPTLC1 gene. The SPTLC1 protein is part of the SPT enzyme which is a ubiquitously expressed, critical and thus highly regulated endoplasmic reticulum bound membrane enzyme that maintains sphingolipid concentrations and thus contributes to lipid metabolism, signalling, and membrane structural functions. Lipid droplets are dynamic organelles containing sphingolipids and membrane bound proteins surrounding a core of neutral lipids, and thus mediate the intracellular transport of these specific molecules. Current literature suggests that there are increased numbers of lipid droplets and alterations of lipid metabolism in a variety of other autosomal dominant neurodegenerative diseases, including Alzheimer's and Parkinson's disease. This study establishes for the first time, a significant increase in the presence of lipid droplets in HSN-1 patient-derived lymphoblasts, indicating a potential connection between lipid droplets and the pathomechanism of HSN-1. However, the expression of adipophilin (ADFP), which has been implicated in the regulation of lipid metabolism, was not altered in lipid droplets from the HSN-1 patient-derived lymphoblasts. This appears to be the first report of increased lipid body accumulation in a peripheral neuropathy, suggesting a fundamental molecular linkage between a number of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background & Aims: Adult hepatocytes undergo cell cycle progression and proliferation in response to partial hepatectomy (PH). Transient lipid accumulation within hepatocytes preceding the peak proliferative phase is a characteristic feature of regenerating livers. However, the molecular mediators and mechanisms responsible for lipid accumulation in regenerating livers are not well understood. Adipose differentiation related protein (ADRP; Plin2) regulates hepatic triglyceride storage and Plin2-deficient (Plin2 −/−) mice have significantly reduced triglyceride (TG) content in the liver. We sought to determine the functional significance of PLIN2 in liver regeneration in response to PH and toxic liver injury and examined whether absence of Plin2 expression modulates hepatocyte proliferation and liver regeneration. Methods: We subjected wild-type (WT) and Plin2 −/− mice to 70% PH or acute carbon tetrachloride (CCL4) treatment and examined the hepatic lipid content, the expression profile of lipid metabolism-related genes, the rate of cellular proliferation and the dynamics of liver regeneration in the treated animals. Results: In response to PH, Plin2 −/− mice showed decreased hepatic triglyceride accumulation and delayed cell cycle progression, which was associated with impaired liver regeneration. Fatty acid (FA) synthesis and lipid transfer gene expression profile were comparable between Plin2 −/− and wild-type mice, while VLDL secretion rate was higher in the Plin2 −/− mice. Downregulated β-oxidation and reduced cytosolic FA level in Plin2 −/− mice may have contributed to the attenuation of the liver regeneration capacity in these animals. In parallel experiments, we also observed attenuated hepatic lipid accumulation and proliferation in response to CCl4-mediated acute toxic liver injury in Plin2 −/− mice. Conclusions: We conclude that PLIN2-mediated lipid accumulation and utilization by the liver is important for efficient liver regeneration in response to PH and toxic liver injury. [Copyright &y& Elsevier]

Proteins that coat the lipid droplets (also known as PAT proteins or perilipin (PLIN) family proteins) have diverse functions that are not well elucidated in many tissues. In skeletal muscle, there is even less known about the functions or characteristics of these proteins or how they might change in response to perturbations that alter both intramyocellular lipid (IMCL) content and fat utilization and oxidation. Therefore, the purpose of this study was to examine the human muscle content and gene expression of the four skeletal muscle PLIN proteins in both lean and obese men and women and how this was changed following a 12-week endurance training protocol. PLIN2-PLIN5 proteins were all more abundant in women than in men ( p = 0.037 and p < 0.0001, respectively), consistent with higher IMCL content observed in female skeletal muscle. PLIN5 (previously known as OXPAT) is of particular interest because it has previously been associated primarily with oxidative tissues that rely heavily on fat oxidation for energy production. Although PLIN5 was not different between lean and obese subjects, it was the only PLIN protein to increase in response to endurance training in both sexes. PLIN5 correlated with IMCL volume ( p < 0.0001), but in general, the other PLIN proteins did not correlate well with IMCL volume, suggesting that the relationship between lipid accumulation and PLIN family protein content is not a simple one. Although more work is necessary, it is clear that PLIN5 likely plays an important role in IMCL accumulation and oxidation, both of which increase with endurance training in human skeletal muscle. [ABSTRACT FROM AUTHOR]

Abstract: Long-chain polyunsaturated fatty acids (LCPUFAs) such as docosahexaenoic acid (DHA) and arachidonic acid (AA) are essential for proper development of fetal brain and retina. These LCPUFAs are selectively enriched in the fetal circulation compared with the maternal circulation. In the current study we investigated the transfer of LCPUFAs and a non-essential fatty acid (oleic acid, OA) in a transwell monolayer system of placental choriocarcinoma (BeWo) cells. We show that incubation with OA results in increased triglyceride accumulation and lipid droplet formation compared with that of DHA. The relative amount of transfer of DHA across the cell monolayer was ∼4-fold greater compared with that of OA when these fatty acids were added individually at 100 μM. This reflects the different fates of these two fatty acids in their metabolism and subsequent transport across the placental trophoblasts to the fetus. When using a mixture of fatty acids mimicking the composition of plasma non-esterified fatty acids during the last trimester of pregnancy, the transfer of OA and the LCPUFAs (DHA and AA) into the basolateral reservoir was not significantly different, whereas the transfer of palmitic acid (PA) was ∼3.5-fold higher than OA transfer. However, since the concentration of OA compared to LCPUFAs was 10-fold higher in the donor chamber, the relative transport of the LCPUFAs was higher compared with that of OA. In addition, we show that inhibiting esterification of fatty acids into acyl-CoA can modulate, in part, the degree of transport through the cells. In conclusion, the transwell model system closely mimics the mechanisms of differential fatty acid transport as observed in vivo. LCPUFAs were transported through the cells more efficiently than shorter fatty acids such as OA. [Copyright &y& Elsevier]

The article presents a study concerning the role of adipose differentiation-related protein (ADFP) in the regulation of foam cell formation and atherosclerosis. The study showed that ADFP gene inactivation in apolipoprotein E-deficient mice reduces the number of lipid droplets in foam cells in atherosclerotic lesions and protects against atherosclerosis. It determines that ADFP inactivation in apolipoprotein E-deficient protects against atherosclerosis and a model of foam cell formation.

Abstract: The PAT family (originally named for Perilipin, ADFP and TIP47) now includes four members: Perilipins, ADFP, TIP47 and S3-12. Significant primary sequence homology and the ability to associate with lipid storage droplets (LSDs) are well conserved within this family and across species. In this study, we have characterized a novel PAT protein, lipid storage droplet protein 5 (LSDP5) of 463 residues. A detailed sequence analysis of all murine PAT proteins reveals that LSDP5, TIP47 and ADFP share the highest order of sequence similarity, whereas perilipin and S3-12 have more divergent carboxyl- and amino-termini, respectively. Ectopically-expressed YFP-LSDP5 or flag-LSDP5 fusion proteins associate with LSDs. In accord with recent published data for perilipin, forced expression of LSDP5 in CHO cells inhibits lipolysis of intracellular LSDs. The LSDP5 gene is primarily transcribed in cells that actively oxidize fatty acids, such as heart, red muscle and liver. Expression of LSDP5 is stimulated by ligand activation of peroxisomal proliferator-activated receptor alpha (PPARα), and significantly reduced in liver and heart in the absence of this transcription factor. PPARα is generally required for regulation of fatty acid metabolism during fasting, but fasting induces LSDP5 mRNA in liver even in the absence of PPARα. [Copyright &y& Elsevier]

ABSTRACT Quantitative RT-PCR was applied to measure the relative expression levels of the adipose differentiation-related protein (ADFP) gene, fatty acid transport protein 1 (FATP1) gene and apolipoprotein B (ApoB) gene in subcutaneous fat, abdominal fat, liver and muscle at five growth stages (28, 49, 70, 91 and 112 d) to determine the effect of the expression ofthese genes on fat deposition in Daweishan Mini chickens.The relative expression of ADFP gene mRNA in the abdominal fat andthe liver was significantly different between 49 d and 70 d (p

Hepatitis B virus X protein (HBx) participates in the occurrence and development processes of hepatocellular carcinoma (HCC) as a multifunctional regulation factor. However, the underlying molecular mechanism remains obscure. Here, we describe the use of p21HBx/+ mouse and SILAM (Stable Isotope Labeling in Mammals) strategy to define the pathological mechanisms for the occurrence and development of HBx induced liver cancer. We systematically compared a series of proteome samples from regular mice, 12- and 24-month old p21HBx/+ mice representing the inflammation and HCC stages of liver disease respectively and their nontransgenic wild-type (WT) littermates. Totally we identified 22 and 97 differentially expressed proteins out of a total of 2473 quantified proteins. Bioinformatics analysis suggested that the lipid metabolism and CDC42-induced cytoskeleton remodeling pathways were strongly activated by the HBx transgene. Interestingly, the protein-protein interaction MS study revealed that HBx directly interacted with multiple proteins in these two pathways. The same effect of up-regulation of cytoskeleton and lipid metabolism related proteins, including CDC42, CFL1, PPARγ and ADFP, was also observed in the Huh-7 cells transfected with HBx. More importantly, CFL1 and ADFP were specifically accumulated in HBV-associated HCC (HBV-HCC) patient samples, and their expression levels were positively correlated with the severity of HBV-related liver disease. These results provide evidence that HBx induces the dysregulation of cytoskeleton remodeling and lipid metabolism and leads to the occurrence and development of liver cancer. The CFL1 and ADFP might be served as potential biomarkers for prognosis and diagnosis of HBV-HCC.

Clear cell renal cell carcinoma (ccRCC) is composed of cells whose cytoplasm filled with lipid droplets, subcellular organelles coated with adipocyte differentiation-related protein (ADFP) for the storage of triacylglycerol converted from excess free fatty acids. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles such as lipid droplets. MAP1S (originally named C19ORF5) is an autophagy activator and promotes the biogenesis and degradation of autophagosomes. Previously, we reported that MAP1S suppresses hepatocellular carcinogenesis in a mouse model and promoted the survival of patients with prostate adenocarcinomas by increasing the degradation of aggregated proteins and dysfunctional mitochondria. Here we show that a suppression of MAP1S in renal cells causes an impairment of autophagic clearance of lipid droplets. In contrast, an overexpression of MAP1S causes an activation of autophagy flux and a reduction of lipid droplets so less DNA double strand breakage is induced. The levels of MAP1S in normal renal cells are dramatically higher than those in the ccRCC tissues and cell lines derived from renal cell carcinomas. High levels of MAP1S are associated with a reduced malignancy and metastasis of ccRCC and predict a better survival of ccRCC patients. Therefore, autophagy defects in the degradation of lipid droplets triggered by the MAP1S deficiency may enhance the initiation and development of ccRCC and reduce the survival of ccRCC patients.